Expression of Macrophage Scavenger Receptor (MSR1) in Peripheral Blood Cells from Patients with Different Respiratory Diseases: Beyond Monocytes.

BACKGROUND: Macrophage scavenger receptor 1 (MSR1) has mostly been described in macrophages, but we previously found a significant gene expression increase in peripheral blood mononuclear cells (PBMCs) of asthmatic patients. OBJECTIVE: To confirm those results and to define its cellular origin in PBMCs. METHODS: Four groups of subjects were studied: healthy controls (C), nonallergic asthmatic (NA), allergic asthmatic (AA), and chronic obstructive pulmonary disease (COPD) patients. RNA was extracted from PBMCs. MSR1 gene expression was analyzed by RT-qPCR. The presence of MSR1 on the cellular surface of PBMC cellular subtypes was analyzed by confocal microscopy and flow cytometry. RESULTS: MSR1 gene expression was significantly increased in the three clinical conditions compared to the healthy control group, with substantial variations according to disease type and severity. MSR1 expression on T cells (CD4+ and CD8+), B cells, and monocytes was confirmed by confocal microscopy and flow cytometry. In all clinical groups, the four immune cell subtypes studied expressed MSR1, with a greater expression on B lymphocytes and monocytes, exhibiting differences according to disease and severity. CONCLUSIONS: This is the first description of MSR1's presence on lymphocytes' surfaces and reinforces the potential role of MSR1 as a player in asthma and COPD.

Documento internacional de consenso sobre apnea obstructiva del sueño / International Consensus Document on Obstructive Sleep Apnea

El objetivo principal de este documento internacional de consenso sobre apnea obstructiva del sueño es proporcionar unas directrices que permitan a los profesionales sanitarios tomar las mejores decisiones en la asistencia de los pacientes adultos con esta enfermedad según un resumen crítico de la literatura más actualizada. El grupo de trabajo de expertos se ha constituido principalmente por 17 sociedades científicas y 56 especialistas con amplia representación geográfica (con la participación de 4 sociedades internacionales), además de un metodólogo experto y un documentalista del Centro Cochrane Iberoamericano. El documento consta de un manuscrito principal, con las novedades más relevantes, y una serie de manuscritos online que recogen las búsquedas bibliográficas sistemáticas de cada uno de los apartados del documento internacional de consenso. Este documento no cubre la edad pediátrica ni el manejo del paciente en ventilación mecánica crónica no invasiva (que se publicarán en sendos documentos de consenso aparte). Palabras clave: Apnea obstructiva del sueño Diagnóstico Tratamiento

The main aim of this international consensus document on obstructive sleep apnea is to provide guidelines based on a critical analysis of the latest literature to help health professionals make the best decisions in the care of adult patients with this disease. The expert working group was formed primarily of 17 scientific societies and 56 specialists from a wide geographical area (including the participation of 4 international societies), an expert in methodology, and a documentalist from the Iberoamerican Cochrane Center. The document consists of a main section containing the most significant innovations and a series of online manuscripts that report the systematic literature searches performed for each section of the international consensus document. This document does not discuss pediatric patients or the management of patients receiving chronic non-invasive mechanical ventilation (these topics will be addressed in separate consensus documents). Keywords: Obstructive sleep apnea Diagnosis Treatment

International Consensus Document on Obstructive Sleep Apnea. / Documento internacional de consenso sobre apnea obstructiva del sueño.

The main aim of this international consensus document on obstructive sleep apnea is to provide guidelines based on a critical analysis of the latest literature to help health professionals make the best decisions in the care of adult patients with this disease. The expert working group was formed primarily of 17 scientific societies and 56 specialists from a wide geographical area (including the participation of 4 international societies), an expert in methodology, and a documentalist from the Iberoamerican Cochrane Center. The document consists of a main section containing the most significant innovations and a series of online manuscripts that report the systematic literature searches performed for each section of the international consensus document. This document does not discuss pediatric patients or the management of patients receiving chronic non-invasive mechanical ventilation (these topics will be addressed in separate consensus documents).

First and Second Waves of Coronavirus Disease 2019 in Madrid, Spain: Clinical Characteristics and Hematological Risk Factors Associated With Critical/Fatal Illness.

OBJECTIVES: This study aims to determine similarities and differences in clinical characteristics between the patients from two waves of severe acute respiratory syndrome coronavirus-2 infection at the time of hospital admission, as well as to identify risk biomarkers of coronavirus disease 2019 severity. DESIGN: Retrospective observational study. SETTING: A single tertiary-care center in Madrid. PATIENTS: Coronavirus disease 2019 adult patients admitted to hospital from March 4, 2020, to March 25, 2020 (first infection wave), and during July 18, 2020, and August 20, 2020 (second infection wave). INTERVENTIONS: Treatment with a hospital-approved drug cocktail during hospitalization. MEASUREMENTS AND MAIN RESULTS: Demographic, clinical, and laboratory data were compared between the patients with moderate and critical/fatal illness across both infection waves. The median age of patients with critical/fatal coronavirus disease 2019 was 67.5 years (interquartile range, 56.75-78.25 yr; 64.5% male) in the first wave and 59.0 years (interquartile range, 48.25-80.50 yr; 70.8% male) in the second wave. Hypertension and dyslipidemia were major comorbidities in both waves. Body mass index over 25 and presence of bilateral pneumonia were common findings. Univariate logistic regression analyses revealed an association of a number of blood parameters with the subsequent illness progression and severity in both waves. However, some remarkable differences were detected between both waves that prevented an accurate extrapolation of prediction models from the first wave into the second wave. Interleukin-6 and d-dimer concentrations at the time of hospital admission were remarkably higher in patients who developed a critical/fatal condition only during the first wave (p < 0.001), although both parameters significantly increased with disease worsening in follow-up studies from both waves. Multivariate analyses from wave 1 rendered a predictive signature for critical/fatal illness upon hospital admission that comprised six blood biomarkers: neutrophil-to-lymphocyte ratio (≥ 5; odds ratio, 2.684 [95% CI, 1.143-6.308]), C-reactive protein (≥ 15.2 mg/dL; odds ratio, 2.412 [95% CI, 1.006-5.786]), lactate dehydrogenase (≥ 411.96 U/L; odds ratio, 2.875 [95% CI, 1.229-6.726]), interleukin-6 (≥ 78.8 pg/mL; odds ratio, 5.737 [95% CI, 2.432-13.535]), urea (≥ 40 mg/dL; odds ratio, 1.701 [95% CI, 0.737-3.928]), and d-dimer (≥ 713 ng/mL; odds ratio, 1.903 [95% CI, 0.832-4.356]). The predictive accuracy of the signature was 84% and the area under the receiver operating characteristic curve was 0.886. When the signature was validated with data from wave 2, the accuracy was 81% and the area under the receiver operating characteristic curve value was 0.874, albeit most biomarkers lost their independent significance. Follow-up studies reassured the importance of monitoring the biomarkers included in the signature, since dramatic increases in the levels of such biomarkers occurred in critical/fatal patients over disease progression. CONCLUSIONS: Most parameters analyzed behaved similarly in the two waves of coronavirus disease 2019. However, univariate logistic regression conducted in both waves revealed differences in some parameters associated with poor prognosis in wave 1 that were not found in wave 2, which may reflect a different disease stage of patients on arrival to hospital. The six-biomarker predictive signature reported here constitutes a helpful tool to classify patient's prognosis on arrival to hospital.

Serum microRNAs as Tool to Predict Early Response to Benralizumab in Severe Eosinophilic Asthma.

Severe eosinophilic asthma poses a serious health and economic problem, so new therapy approaches have been developed to control it, including biological drugs such as benralizumab, which is a monoclonal antibody that binds to IL-5 receptor alpha subunit and depletes peripheral blood eosinophils rapidly. Biomarkers that predict the response to this drug are needed so that microRNAs (miRNAs) can be useful tools. This study was performed with fifteen severe eosinophilic asthmatic patients treated with benralizumab, and serum miRNAs were evaluated before and after treatment by semi-quantitative PCR (qPCR). Patients showed a clinical improvement after benralizumab administration. Additionally, deregulation of miR-1246, miR-5100 and miR-338-3p was observed in severe asthmatic patients after eight weeks of therapy, and a correlation was found between miR-1246 and eosinophil counts, including a number of exacerbations per year in these severe asthmatics. In silico pathway analysis revealed that these three miRNAs are regulators of the MAPK signaling pathway, regulating target genes implicated in asthma such as NFKB2, NFATC3, DUSP1, DUSP2, DUSP5 and DUSP16. In this study, we observed an altered expression of miR-1246, miR-5100 and miR-338-3p after eight weeks of benralizumab administration, which could be used as early response markers.

Patient Management Assisted by a Neural Network Reduces Mortality in an Intermediate Care Unit / El manejo del paciente asistido por una red neuronal disminuye la mortalidad en una unidad de cuidados intermedios

INTRODUCTION: Mortality risk prediction for Intermediate Respiratory Care Unit's (IRCU) patients can facilitate optimal treatment in high-risk patients. While Intensive Care Units (ICUs) have a long term experience in using algorithms for this purpose, due to the special features of the IRCUs, the same strategics are not applicable. The aim of this study is to develop an IRCU specific mortality predictor tool using machine learning methods. METHODS: Vital signs of patients were recorded from 1966 patients admitted from 2007 to 2017 in the Jiménez Díaz Foundation University Hospital's IRCU. A neural network was used to select the variables that better predict mortality status. Multivariate logistic regression provided us cut-off points that best discriminated the mortality status for each of the parameters. A new guideline for risk assessment was applied and mortality was recorded during one year. RESULTS: Our algorithm shows that thrombocytopenia, metabolic acidosis, anemia, tachypnea, age, sodium levels, hypoxemia, leukocytopenia and hyperkalemia are the most relevant parameters associated with mortality. First year with this decision scene showed a decrease in failure rate of a 50%. CONCLUSIONS: We have generated a neural network model capable of identifying and classifying mortality predictors in the IRCU of a general hospital. Combined with multivariate regression analysis, it has provided us with an useful tool for the real-time monitoring of patients to detect specific mortality risks. The overall algorithm can be scaled to any type of unit offering personalized results and will increase accuracy over time when more patients are included to the cohorts

INTRODUCCIÓN: La predicción del riesgo de mortalidad de los pacientes en la unidad de cuidados respiratorios intermedios (UCRI) puede facilitar un tratamiento óptimo en pacientes de alto riesgo. Si bien las unidades de cuidados intensivos (UCI) tienen una experiencia a largo plazo en el uso de algoritmos para este propósito, debido a las características especiales de las UCRI, no se pueden aplicar las mismas estrategias. El objetivo de este estudio es desarrollar una herramienta de predicción de mortalidad específica para la UCRI utilizando métodos de aprendizaje automático. MÉTODOS: Se registraron los signos vitales de 1.966 pacientes ingresados entre 2007 y 2017 en la UCRI del Hospital Universitario de la Fundación Jiménez Díaz. Se utilizó una red neuronal para seleccionar las variables que mejor predijeran el estado de mortalidad. La regresión logística multivariante nos proporcionó los puntos de corte que discriminaban mejor el estado de la mortalidad para cada uno de los parámetros. Se aplicó una nueva guía para la evaluación de riesgos, y se registró la mortalidad durante un año. RESULTADOS: Nuestro algoritmo muestra que la trombocitopenia, la acidosis metabólica, la anemia, la taquipnea, la edad, los niveles de sodio, la hipoxemia, la leucocitopenia y la hipercalemia son los parámetros más relevantes asociados con la mortalidad. En el primer año con este escenario de decisión se mostró una disminución en la tasa de fracaso de un 50%. CONCLUSIONES: Hemos generado un modelo de red neuronal capaz de identificar y clasificar predictores de mortalidad en la UCRI de un hospital general. Combinado con el análisis de regresión multivariante, nos ha proporcionado una herramienta útil para la monitorización en tiempo real de pacientes para detectar riesgos de mortalidad específicos. El algoritmo general se puede modificar a escala para cualquier tipo de unidad, lo que ofrecerá resultados personalizados, y su precisión aumentará con el tiempo, según se incluyan más pacientes en las cohortes

Early detection of skeletal muscle bioenergetic deficit by magnetic resonance spectroscopy in cigarette smoke-exposed mice.

Skeletal muscle dysfunction is a common complication and an important prognostic factor in patients with chronic obstructive pulmonary disease (COPD). It is associated with intrinsic muscular abnormalities of the lower extremities, but it is not known whether there is an easy way to predict its presence. Using a mouse model of chronic cigarette smoke exposure, we tested the hypothesis that magnetic resonance spectroscopy allows us to detect muscle bioenergetic deficit in early stages of lung disease. We employed this technique to evaluate the synthesis rate of adenosine triphosphate (ATP) and characterize concomitant mitochondrial dynamics patterns in the gastrocnemius muscle of emphysematous mice. The fibers type composition and citrate synthase (CtS) and cytochrome c oxidase subunit IV (COX4) enzymatic activities were evaluated. We found that the rate of ATP synthesis was reduced in the distal skeletal muscle of mice exposed to cigarette smoke. Emphysematous mice showed a significant reduction in body weight gain, in the cross-sectional area of the total fiber and in the COX4 to CtS activity ratio, due to a significant increase in CtS activity of the gastrocnemius muscle. Taken together, these data support the hypothesis that in the early stage of lung disease, we can detect a decrease in ATP synthesis in skeletal muscle, partly caused by high oxidative mitochondrial enzyme activity. These findings may be relevant to predict the presence of skeletal bioenergetic deficit in the early stage of lung disease besides placing the mitochondria as a potential therapeutic target for the treatment of COPD comorbidities.

Patient Management Assisted by a Neural Network Reduces Mortality in an Intermediate Care Unit.

INTRODUCTION: Mortality risk prediction for Intermediate Respiratory Care Unit's (IRCU) patients can facilitate optimal treatment in high-risk patients. While Intensive Care Units (ICUs) have a long term experience in using algorithms for this purpose, due to the special features of the IRCUs, the same strategics are not applicable. The aim of this study is to develop an IRCU specific mortality predictor tool using machine learning methods. METHODS: Vital signs of patients were recorded from 1966 patients admitted from 2007 to 2017 in the Jiménez Díaz Foundation University Hospital's IRCU. A neural network was used to select the variables that better predict mortality status. Multivariate logistic regression provided us cut-off points that best discriminated the mortality status for each of the parameters. A new guideline for risk assessment was applied and mortality was recorded during one year. RESULTS: Our algorithm shows that thrombocytopenia, metabolic acidosis, anemia, tachypnea, age, sodium levels, hypoxemia, leukocytopenia and hyperkalemia are the most relevant parameters associated with mortality. First year with this decision scene showed a decrease in failure rate of a 50%. CONCLUSIONS: We have generated a neural network model capable of identifying and classifying mortality predictors in the IRCU of a general hospital. Combined with multivariate regression analysis, it has provided us with an useful tool for the real-time monitoring of patients to detect specific mortality risks. The overall algorithm can be scaled to any type of unit offering personalized results and will increase accuracy over time when more patients are included to the cohorts.

Análisis de costes y mortalidad de una unidad de cuidados intermedios respiratorios. ¿Es realmente eficiente y segura? / Cost and Mortality Analysis of an Intermediate Respiratory Care Unit. Is It Really Efficient and Safe?

Introducción: Históricamente se ha asumido que las unidades de cuidados intermedios respiratorios (UCIR) eran estructuras eficientes por los costes evitados atribuibles a la reducción de los ingresos en las unidades de cuidados intensivos (UCI) y eficaces por la especialización neumológica. Métodos: Se evaluó el número de ingresos y mortalidad en la unidad, histórica y en el año 2016. Ese año además se describieron los grupos relacionados de diagnóstico (GRD) agrupados y el coste evitado por estancia en UCI en relación con todos los capítulos presupuestarios. Se realizó un análisis multivariante para asociar costes a pesos medios y complejidad y se realizó una regresión logística múltiple sobre la totalidad de enfermos ingresados de 2004 a 2017 para describir las variables asociadas a la mortalidad en nuestra unidad. Resultados: La UCIR evita un coste al hospital de 500.000 €/año al reducir días de estancia en las UCI. El análisis sobre la cohorte de 2016 describe que los costes se asocian al peso medio y mortalidad, y por tanto, a la complejidad. El análisis de regresión logística multivariante sobre la cohorte de 2004-2017 describe la frecuencia respiratoria, la leucopenia, la anemia, la hiperpotasemia y la acidosis como las variables que mejor se asocian con la mortalidad. El área bajo la curva para el modelo logístico fue de 0,75. Conclusión: La UCIR analizada ha demostrado ser eficiente en términos de «coste evitado» y ahorro ligado a la complejidad. Nuestros resultados sugieren que las UCIR son un entorno seguro para los pacientes al tener una mortalidad menor que otras unidades similares

Introduction: Historically, it has been assumed that Intermediate Respiratory Care Units (IRCU) were efficient, because they saved costs by reducing the number of admissions to intensive care units (ICU), and effective, because they specialized in respiratory diseases. Methods: The number of IRCU admissions and mortality rate, historically and in 2016, were evaluated. For 2016, the grouped Related Diagnostic Groups (DRGs) were also described, and the savings achieved under all budgetary headings by avoiding UCI stays were calculated. A multivariate analysis was performed to associate costs with mean weights and complexity, and multiple logistic regression was performed on all patients admitted from 2004 to 2017 to describe the variables associated with mortality in our unit. Results: An IRCU generates savings of 500,000 €/year by reducing length of ICU stay. Analysis of the 2016 cohort shows that costs correlate with mean weight and mortality, and consequently complexity. The multivariate logistic regression analysis of the 2004-2017 cohort found respiratory frequency, leukopenia, anemia, hyperkalemia, and acidosis to be the variables best associated with mortality. The area under the curve for the logistic model was 0.75. Conclusion: The IRCU analyzed in our study was efficient in terms of "avoided costs" and savings associated with complexity. Our results suggest that IRCUs have a lower mortality rate than other similar units, and are therefore a safe environment for patients

Cost and Mortality Analysis of an Intermediate Respiratory Care Unit. Is It Really Efficient and Safe? / Análisis de costes y mortalidad de una unidad de cuidados intermedios respiratorios. ¿Es realmente eficiente y segura?

INTRODUCTION: Historically, it has been assumed that Intermediate Respiratory Care Units (IRCU) were efficient, because they saved costs by reducing the number of admissions to intensive care units (ICU), and effective, because they specialized in respiratory diseases. METHODS: The number of IRCU admissions and mortality rate, historically and in 2016, were evaluated. For 2016, the grouped Related Diagnostic Groups (DRGs) were also described, and the savings achieved under all budgetary headings by avoiding UCI stays were calculated. A multivariate analysis was performed to associate costs with mean weights and complexity, and multiple logistic regression was performed on all patients admitted from 2004 to 2017 to describe the variables associated with mortality in our unit. RESULTS: An IRCU generates savings of €500,000/year by reducing length of ICU stay. Analysis of the 2016 cohort shows that costs correlate with mean weight and mortality, and consequently complexity. The multivariate logistic regression analysis of the 2004-2017 cohort found respiratory frequency, leukopenia, anemia, hyperkalemia, and acidosis to be the variables best associated with mortality. The area under the curve for the logistic model was 0.75. CONCLUSION: The IRCU analyzed in our study was efficient in terms of 'avoided costs' and savings associated with complexity. Our results suggest that IRCUs have a lower mortality rate than other similar units, and are therefore a safe environment for patients.

Obstructive sleep apnea and nocturnal hypoxemia are associated with an increased risk of lung cancer.

STUDY OBJECTIVES: To identify a link between sleep disordered breathing, nocturnal hypoxemia, and lung cancer. METHODS: We conducted a cross-sectional study of a combined cohort of 302 individuals derived from the sleep apnea in lung cancer study (SAIL; NCT02764866) investigating the prevalence of sleep apnea in lung cancer, and the sleep apnea in lung cancer screening study (SAILS; NCT02764866) investigating the prevalence of sleep apnea in a lung cancer screening program. All subjects had spirometry and a chest CT, underwent home sleep apnea testing (HSAT), and completed a sleep related questionnaire. Subjects from the SAIL study underwent HSAT prior to initiating oncologic therapy or surgery. Subjects with an apnea-hypopnea index (AHI) > 15 were compared with a control group of individuals with an AHI < 15. Propensity score, near neighbor matching, and logistic regression adjusted for potential confounders, were used in order to evaluate the association between sleep apnea, the AHI, oxygen desaturation indices and lung cancer. RESULTS: The prevalence of sleep apnea and lung cancer in the combined cohort was 42% and 21%, respectively. Lung cancer was 8% more prevalent in patients with an AHI >15. The difference was statistically significant when assessed by propensity score matching (p = 0.015) and nearest neighbor matching (p = 0.041). Binary logistic regression adjusted for potential confounders revealed a statistically significant association between AHI (p = 0.04), nocturnal hypoxemia, including time spent below 90% oxyhemoglobin saturation (T90%; p = 0.005), 3% oxygen desaturation index (ODI3; p = 0.02) and lung cancer. CONCLUSIONS: Sleep apnea and nocturnal hypoxemia are associated with an increased prevalence of lung cancer. CLINICAL TRIAL REGISTRATION: SAIL study (NCT02764866) and SAILS study (NCT02764866).

Continuous monitoring of intrinsic PEEP based on expired CO2 kinetics: an experimental validation study.

BACKGROUND: Quantification of intrinsic PEEP (PEEPi) has important implications for patients subjected to invasive mechanical ventilation. A new non-invasive breath-by-breath method (etCO2D) for determination of PEEPi is evaluated. METHODS: In 12 mechanically ventilated pigs, dynamic hyperinflation was induced by interposing a resistance in the endotracheal tube. Airway pressure, flow, and exhaled CO2 were measured at the airway opening. Combining different I:E ratios, respiratory rates, and tidal volumes, 52 different levels of PEEPi (range 1.8-11.7 cmH2O; mean 8.45 ± 0.32 cmH2O) were studied. The etCO2D is based on the detection of the end-tidal dilution of the capnogram. This is measured at the airway opening by means of a CO2 sensor in which a 2-mm leak is added to the sensing chamber. This allows to detect a capnogram dilution with fresh air when the pressure coming from the ventilator exceeds the PEEPi. This method was compared with the occlusion method. RESULTS: The etCO2D method detected PEEPi step changes of 0.2 cmH2O. Reference and etCO2D PEEPi presented a good correlation (R2 0.80, P < 0.0001) and good agreement, bias - 0.26, and limits of agreement ± 1.96 SD (2.23, - 2.74) (P < 0.0001). CONCLUSIONS: The etCO2D method is a promising accurate simple way of continuously measure and monitor PEEPi. Its clinical validity needs, however, to be confirmed in clinical studies and in conditions with heterogeneous lung diseases.

Diagnostic accuracy of nasal cannula versus microphone for detection of snoring.

OBJECTIVE: Snoring is a common reason for referral to a sleep unit. Although there are several instruments to measure snoring, there is no gold standard for this purpose. In this study, we determine the diagnostic accuracy of the cannula as compared with the microphone, which are the two most commonly used tools. STUDY DESIGN: We performed a cross-sectional study of 75 patients who underwent baseline home sleep apnea testing for any reason. METHODS: Snore intensity and percentage were assessed during Home sleep-apnea testing via nasal cannula and microphone in all patients. We performed a complete diagnostic accuracy analysis, assuming the microphone to be the reference instrument use in order to compare it with the cannula. RESULTS: The intra-class correlation coefficient between the cannula and microphone for the percentage of snoring was 0.25. The Bland Bland-Altman analysis to determine the agreement regarding the percentage of snoring showed a lower limit of -57.73 and an upper limit of 20.30. A linear regression analysis of the differences produced a negative slope of -0.86. The receiver operating characteristic curve for severe snoring using the cannula produced an area under the curve of 0.67 (P = 0.019). The cannula showed a sensitivity of 57.89 and a specificity of 73.21. CONCLUSION: The nasal cannula showed poor reliability and accuracy for measuring snoring. LEVEL OF EVIDENCE: 2b. Laryngoscope, 127:2886-2890, 2017.

Non-invasive ventilation in obesity hypoventilation syndrome without severe obstructive sleep apnoea.

BACKGROUND: Non-invasive ventilation (NIV) is an effective form of treatment in patients with obesity hypoventilation syndrome (OHS) who have concomitant severe obstructive sleep apnoea (OSA). However, there is a paucity of evidence on the efficacy of NIV in patients with OHS without severe OSA. We performed a multicentre randomised clinical trial to determine the comparative efficacy of NIV versus lifestyle modification (control group) using daytime arterial carbon dioxide tension (PaCO2) as the main outcome measure. METHODS: Between May 2009 and December 2014 we sequentially screened patients with OHS without severe OSA. Participants were randomised to NIV versus lifestyle modification and were followed for 2 months. Arterial blood gas parameters, clinical symptoms, health-related quality of life assessments, polysomnography, spirometry, 6-min walk distance test, blood pressure measurements and healthcare resource utilisation were evaluated. Statistical analysis was performed using intention-to-treat analysis. RESULTS: A total of 365 patients were screened of whom 58 were excluded. Severe OSA was present in 221 and the remaining 86 patients without severe OSA were randomised. NIV led to a significantly larger improvement in PaCO2 of -6 (95% CI -7.7 to -4.2) mm Hg versus -2.8 (95% CI -4.3 to -1.3) mm Hg, (p<0.001) and serum bicarbonate of -3.4 (95% CI -4.5 to -2.3) versus -1 (95% CI -1.7 to -0.2 95% CI)  mmol/L (p<0.001). PaCO2 change adjusted for NIV compliance did not further improve the inter-group statistical significance. Sleepiness, some health-related quality of life assessments and polysomnographic parameters improved significantly more with NIV than with lifestyle modification. Additionally, there was a tendency towards lower healthcare resource utilisation in the NIV group. CONCLUSIONS: NIV is more effective than lifestyle modification in improving daytime PaCO2, sleepiness and polysomnographic parameters. Long-term prospective studies are necessary to determine whether NIV reduces healthcare resource utilisation, cardiovascular events and mortality. TRIAL REGISTRATION NUMBER: NCT01405976; results.

Eficacia a medio y largo plazo de la ventilación no invasiva en el síndrome de hipoventilación-obesidad (estudio Pickwick) / Mid- and Long-Term Efficacy of Non-Invasive Ventilation in Obesity Hypoventilation Syndrome: The Pickwick's Study

El proyecto Pickwick es un estudio prospectivo, aleatorizado, abierto y controlado con grupos en paralelo que intenta dar respuesta a los interrogantes del síndrome de hipoventilación-obesidad (SHO), una enfermedad creciente en los países desarrollados. Para ello, pacientes con SHO fueron divididos en pacientes con índice de apneas-hipoapneas (IAH) ≥30 y <30 mediante polisomnografía. El grupo con IAH≥30 se aleatorizó a tratamiento mediante estilo de vida saludable, ventilación no invasiva (VNI) o presión en la vía aérea positiva continua (CPAP). El grupo con IAH<30, a VNI o estilo de vida saludable. Su objetivo ha sido evaluar la eficacia del tratamiento con ventilación VNI, CPAP y estilo de vida saludable (control) a medio y largo plazo en el SHO, analizando como variable primaria la PaCO2 y los días de hospitalización, respectivamente, y como variables operativas el porcentaje de abandonos por razones médicas y mortalidad. Los objetivos secundarios a medio plazo fueron: 1) evaluar la eficacia clínica-funcional, en calidad de vida, en variables polisomnográficas y ecocardiográficas; 2) investigar la importancia de los episodios apneicos y de la leptina en la génesis de la hipoventilación alveolar diurna y el cambio con los diferentes tratamientos; 3) investigar si las alteraciones metabólicas, bioquímicas y disfunción endotelial vascular dependen de la presencia de apneas e hipoapneas, y 4) cambio de marcadores inflamatorios y de daño endotelial con los tratamientos. Los objetivos secundarios a largo plazo fueron: 1) evaluar la eficacia clínico-funcional y en calidad de vida con VNI y CPAP; 2) cambio de la leptina, marcadores inflamatorios y de daño endotelial con los tratamientos; 3) cambio de la hipertensión pulmonar y otras variables ecocardiográficas, así como en la hipertensión arterial e incidencia de episodios cardiovasculares, y 4) frecuencia de abandonos y mortalidad

The Pickwick project was a prospective, randomized and controlled study, which addressed the issue of obesity hypoventilation syndrome (OHS), a growing problem in developed countries. OHS patients were divided according to apnea-hypopnea index (AHI) ≥ 30 and < 30 determined by polysomnography. The group with AHI ≥ 30 was randomized to intervention with lifestyle changes, noninvasive ventilation (NIV) or continuous positive airway pressure (CPAP); the group with AHI < 30 received NIV or lifestyle changes. The aim of the study was to evaluate the efficacy of NIV treatment, CPAP and lifestyle changes (control) in the medium and long-term management of patients with OHS. The primary variables were PaCO2 and days of hospitalization, and operating variables were the percentage of dropouts for medical reasons and mortality. Secondary medium-term objectives were: (I) to evaluate clinical-functional effectiveness on quality of life, echocardiographic and polysomnographic variables; (II) to investigate the importance of apneic events and leptin in the pathogenesis of daytime alveolar hypoventilation and change according to the different treatments; (III) to investigate whether metabolic, biochemical and vascular endothelial dysfunction disorders depend on the presence of apneas and hypopneasm and (IV) changes in inflammatory markers and endothelial damage according to treatment. Secondary long-term objectives were to evaluate: (I) clinical and functional effectiveness and quality of life with NIV and CPAP; (II) changes in leptin, inflammatory markers and endothelial damage according to treatment; (III) changes in pulmonary hypertension and other echocardiographic variables, as well as blood pressure and incidence of cardiovascular events, and (IV) dropout rate and mortality

Mid- and Long-Term Efficacy of Non-Invasive Ventilation in Obesity Hypoventilation Syndrome: The Pickwick's Study.

The Pickwick project was a prospective, randomized and controlled study, which addressed the issue of obesity hypoventilation syndrome (OHS), a growing problem in developed countries. OHS patients were divided according to apnea-hypopnea index (AHI) ≥30 and <30 determined by polysomnography. The group with AHI≥30 was randomized to intervention with lifestyle changes, noninvasive ventilation (NIV) or continuous positive airway pressure (CPAP); the group with AHI<30 received NIV or lifestyle changes. The aim of the study was to evaluate the efficacy of NIV treatment, CPAP and lifestyle changes (control) in the medium and long-term management of patients with OHS. The primary variables were PaCO2 and days of hospitalization, and operating variables were the percentage of dropouts for medical reasons and mortality. Secondary medium-term objectives were: (i)to evaluate clinical-functional effectiveness on quality of life, echocardiographic and polysomnographic variables; (ii)to investigate the importance of apneic events and leptin in the pathogenesis of daytime alveolar hypoventilation and change according to the different treatments; (ii)to investigate whether metabolic, biochemical and vascular endothelial dysfunction disorders depend on the presence of apneas and hypopneasm and (iv)changes in inflammatory markers and endothelial damage according to treatment. Secondary long-term objectives were to evaluate: (i)clinical and functional effectiveness and quality of life with NIV and CPAP; (ii)changes in leptin, inflammatory markers and endothelial damage according to treatment; (iii)changes in pulmonary hypertension and other echocardiographic variables, as well as blood pressure and incidence of cardiovascular events, and (iv)dropout rate and mortality.

Efficacy of home single-channel nasal pressure for recommending continuous positive airway pressure treatment in sleep apnea.

INTRODUCTION: Unlike other prevalent diseases, obstructive sleep apnea (OSA) has no simple tool for diagnosis and therapeutic decision-making in primary healthcare. Home single-channel nasal pressure (HNP) may be an alternative to polysomnography for diagnosis but its use in therapeutic decisions has yet to be explored. OBJECTIVES: To ascertain whether an automatically scored HNP apnea-hypopnea index (AHI), used alone to recommend continuous positive airway pressure (CPAP) treatment, agrees with decisions made by a specialist using polysomnography and several clinical variables. METHODS: Patients referred by primary care physicians for OSA suspicion underwent randomized polysomnography and HNP. We analyzed the total sample and both more and less symptomatic subgroups for Bland and Altman plots to explore AHI agreement; receiver operating characteristic curves to establish area under the curve (AUC) measurements for CPAP recommendation; and therapeutic decision efficacy for several HNP AHI cutoff points. RESULTS: Of the 787 randomized patients, 35 (4%) were lost, 378 (48%) formed the more symptomatic and 374 (48%) the less symptomatic subgroups. AHI bias and agreement limits were 5.8 ± 39.6 for the total sample, 5.3 ± 38.7 for the more symptomatic, and 6 ± 40.2 for the less symptomatic subgroups. The AUC were 0.826 for the total sample, 0.903 for the more symptomatic, and 0.772 for the less symptomatic subgroups. In the more symptomatic subgroup, 70% of patients could be correctly treated with CPAP. CONCLUSION: Automatic HNP scoring can correctly recommend CPAP treatment in most of more symptomatic patients with OSA suspicion. Our results suggest that this device may be an interesting tool in initial OSA management for primary care physicians, although future studies in a primary care setting are necessary. CLINICAL TRIALS INFORMATION: Clinicaltrial.gov identifier: NCT01347398.

Terapias ventilatorias domiciliarias en el síndrome de apnea-hipopnea del sueño / Home Ventilation Therapy in Obstructive Sleep Apnea-Hypopnea Syndrome

El síndrome de apnea-hipopnea del sueño es una enfermedad muy prevalente, con tasas altas de infradiagnóstico en el momento actual, que conlleva un elevado impacto sanitario, económico y social, y consume gran parte de los recursos destinados a las terapias respiratorias domiciliarias. Con motivo del Año SEPAR 2014 del paciente crónico y las terapias respiratorias domiciliarias, patrocinado por la Sociedad Española de Neumología y Cirugía Torácica, en este artículo se revisa la literatura más reciente publicada sobre las indicaciones del tratamiento de la apnea del sueño y sus controversias, las últimas evidencias de las indicaciones de los distintos dispositivos de presión positiva, así como los modos de ajuste, desde el uso de fórmulas empíricas o estimaciones matemáticas, a los modernos equipos de auto-CPAP, pasando porla titulación manual como «gold standard». Además, se hace hincapié en la necesidad de seguimiento que los pacientes precisan para asegurar la adherencia y cumplimiento de la terapia. Por último, se comentan someramente otros tratamientos, que no son el objetivo del artículo

Obstructive sleep apnea-hypopnea is a highly prevalent disease that is often underdiagnosed at present. It has a significant economic and social welfare impact, accounting for a large part of the resources assigned to home respiratory therapies. As part of the 2014 SEPAR Year of the Chronic Patient and Domiciliary Respiratory Care sponsored by the Spanish Society of Pulmonology and Thoracic Surgery, this article reviews the most recent publications on the indications and controversial issues in the treatment of sleep apnea, the latest evidence for indication of various positive pressure devices, and adjustment modes, ranging from the use of empirical formulae or mathematical estimations to modern auto-CPAP equipment, while not forgetting the gold standard of manual titration. Emphasis is placed on the need for monitoring required by patients to ensure treatment adherence and compliance. Finally, other therapies that are not the object of this article are briefly reviewed

Proliferative activity of liver growth factor is associated with an improvement of cigarette smoke-induced emphysema in mice.

Cigarette smoke (CS)-induced emphysema is a major component of chronic obstructive pulmonary disease (COPD). COPD treatment is based on the administration of bronchodilators and corticosteroids to control symptoms and exacerbations, however, to date, there are no effective therapies to reverse disease progression. Liver growth factor (LGF) is an albumin-bilirubin complex with mitogenic properties, whose therapeutic effects have previously been reported in a model of emphysema and several rodent models of human disease. To approach the therapeutic effect of LGF in a model of previously established emphysema, morphometric and lung function parameters, matrix metalloproteinase (MMP) activity and the expression of several markers, such as VEGF, PCNA, 3NT and Nrf2, were assessed in air-exposed and CS-exposed C57BL/6J male mice with and without intraperitoneal (i.p.) injection of LGF. CS-exposed mice presented a significant enlargement of alveolar spaces, higher alveolar internal area and loss of lung function that correlated with higher MMP activity, higher expression of 3NT and lower expression of VEGF. CS-exposed mice injected with LGF, showed an amelioration of emphysema and improved lung function, which correlated with lower MMP activity and 3NT expression and higher levels of VEGF, PCNA and Nrf2. Taken together, this study suggests that LGF administration ameliorates CS-induced emphysema, highlights the ability of LGF to promote alveolar cell proliferation and may be a promising strategy to revert COPD progression.